The FDA has approved Merck's Keytruda injection for the treatment of patients with unresectable or metastatic melanoma and disease progression following administration of ipilimumab and, if positive for the BRAF V600 mutation, a BRAF inhibitor.
The FDA has approved Merck’s Keytruda (pembrolizumab) injection for the treatment of patients with unresectable or metastatic melanoma and disease progression following administration of ipilimumab and, if positive for the BRAF V600 mutation, a BRAF inhibitor. The indication received an accelerated approval, which was based on tumor response rate and durability of response. An improvement in survival or diseaserelated symptoms, however, has not yet been established. Ongoing approval for this indication may be contingent upon verification and description of clinical benefits in the confirmatory trials.1 Keytruda is the first medication in its class to be approved for this indication.2
Pharmacology and Pharmacokinetics
Keytruda is a human programmed death receptor-1 (PD-1)-blocking antibody. It binds to the PD-1 receptor and blocks its interaction with the PD-L1 and PD-L2 ligands, causing a release of the PD-1 pathwaymediated inhibition of the immune response, including the antitumor immune response. This results in decreased tumor growth in syngeneic mouse tumor models.
The mean elimination half-life of Keytruda is 26 days. Steady-state levels were reached by 18 weeks of repeated 3-week dosing. Gender, renal impairment, mild hepatic impairment, and tumor burden did not affect the pharmacokinetics of Keytruda.1
Dosage and Administration
Keytruda should be given as a 2-mg/kg intravenous infusion over 30 minutes every 3 weeks. Prior to administration, Keytruda must be diluted in either 0.9% sodium chloride injection or 5% dextrose injection to a final concentration of 1 to 10 mg/mL.1
Keytruda was evaluated in a multicenter, open-label, randomized, dose-comparative, activityestimating cohort of 173 patients with unresectable or metastatic melanoma and disease progression. Key eligibility criteria were unresectable or metastatic melanoma with disease progression; refractory to 2 or more doses of ipilimumab (3 mg/kg or higher) and, if positive for the BRAF V600 mutation, a BRAF or MEK inhibitor; and disease progression within 24 weeks following the last dose of ipilimumab.
Patients were randomized to receive either 2 mg/kg or 10 mg/kg of Keytruda every 3 weeks until unacceptable toxicity or disease progression occurred. Approximately 24% of patients in the 2-mg/ kg group experienced an objective response to treatment. The response lasted at least 1.4 to 8.5 months, with an even longer response period in many patients.1-3
Contraindications, Warnings, and Precautions
There are no contraindications to treatment with Keytruda. If an immune-mediated adverse reaction occurs, corticosteroids may be given based on the severity of the reaction. Withhold Keytruda if moderate immune-mediated pneumonitis occurs, and permanently discontinue the drug if the pneumonitis is severe or life-threatening.
If moderate to severe immunemediated colitis occurs, withhold Keytruda; if the colitis is severe or life-threatening, however, discontinue the drug. If immune-mediated hepatitis occurs, monitor changes in hepatic function and withhold or discontinue Keytruda depending on the severity of liver enzyme elevations.
If moderate immune-mediated hypophysitis occurs, withhold Keytruda; however, discontinue if the hypophysitis is severe, and permanently discontinue it if the condition is life-threatening. If immune-mediated nephritis occurs, monitor changes in renal function and withhold Keytruda if the reaction is moderate; permanently discontinue Keytruda if the nephritis is severe or life-threatening. If immune-mediated hyperthyroidism or hypothyroidism occurs, withhold Keytruda if it is severe and permanently discontinue the drug if the condition is life-threatening.
Keytruda is a Pregnancy Category D drug and should not be used during pregnancy. Women of child-bearing age should be advised to use highly effective contraception during treatment with Keytruda and for at least 4 months following its last dose. Keytruda should also not be used during breast-feeding.
The most common adverse reactions (≥20%) were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea.1
Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.
- Keytruda complete prescribing information. Whitehouse Station, NJ: Merck & Co, Inc; 2014. www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. Accessed February 2015.
- FDA approves Keytruda for advanced melanoma [press release]. Silver Spring, MD: US Food and Drug Administration; September 4, 2014. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm412802.htm. Accessed February 2015.
- Merck receives accelerated approval of Keytruda (pembrolizumab), the first FDA-approved anti-PD-1 therapy. Whitehouse Station, NJ: Merck & Co, Inc; September 4, 2014. www.mercknewsroom.com/news-release/prescription-medicine-news/merck-receives-accelerated-approval-keytruda-pembrolizumab-f. Accessed February 2015.